1. Field of the Invention
The present invention relates to a carboxylic acid derivative having a fused ring and a pharmacologically acceptable salt thereof. More specifically, it relates to a novel carboxylic acid derivative having a fused ring which exhibit agonism for retinoic acid receptors and a pharmacologically acceptable salt thereof.
2. Prior Art
Retinoic acid is a substance essential to the growth and life support of human being and other mammals. It has been known that retinoic acid acts as a morphogenetic factor in ontogenesis and functions variously in the differentiation and proliferation of cells of adults. For example, it has been known that the acid participates in cornification, formation of hair, functions of sebaceous gland and so on with respect to the epidermis, in metabolism of bone and cartilage with respect to the connective tissue, in regulation of immune functions with respect to the immune system, in differentiation of nerve cells with respect to the nervous system, in differentiation and proliferation of blood cells with respect to the hemic system, and in the lipid metabolism, the mineral metabolism and the basal metabolism and so on. These various physiological actions of retinoic acid are exhibited by various control mechanisms through retinoid receptor family present in the cell nucleus, for example, by regulating the expression of transcription activators, by regulating the expression of enzymes such as collagenase, tissue plasminogen activator or tyrosine kinase, or by regulating the production of cytokines such as IL-6.
The connections of the above physiological actions of retinoic acid with various diseases have recently been elucidated gradually, and in particular, differentiation-inducing therapy with all-trans retinoic acid has attracted attention as a new therapeutic method for some cancers such as acute promyelocytic leukemia.
With respect to retinoic acid, however, there have appeared problematic tolerance due to the induction of P450 which is a hepatic metabolic enzyme, adverse effects due to accumulation, and other problems. Under these circumstances there have been expected research and development of novel retinoid-related compounds which can be substituted for retionic acid as preventive and therapeutic drugs for various diseases.